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StrokePhase 3PRISMSNCT02072226

A Study of the Efficacy and Safety of Alteplase in Participants With Mild Stroke

A Phase 3 study testing Alteplase and Aspirin in people with Stroke, run by Genentech, Inc. at 88 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

PRISMS is a double-blind, multicenter, randomized, Phase IIIb study to evaluate the efficacy and safety of intravenous (IV) alteplase in participants with mild acute ischemic strokes that do not appear to be clearly disabling. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Stroke
What is being tested?
Alteplase and Aspirin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
313 participants
Where
88 sitesUnited States
Study dates
31 May 2014to 22 Mar 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Mild ischemic stroke defined as the most recent pre-treatment NIHSS score of less than or equal to(</=) 5 and determined as not clearly disabling by the investigator
  • Study treatment initiated within 3 hours of last time participant seen normal

Who cannot join

  • Computed tomography (CT) or magnetic resonance imaging (MRI) findings of one of the following:
  • CT with clear large hypodensity that is greater than (>) one-third middle cerebral artery (MCA) territory (or >100 cubic centimeter [cc] if not in MCA territory)
  • MRI with clear large hyperintensity on concurrent diffusion-weighted (DW) and fluid-attenuated inversion recovery (FLAIR) that is greater than one-third MCA territory (or greater than 100 cc if not in MCA territory),
  • Imaging lesion consistent with acute hemorrhage, or
  • Evidence of intraparenchymal tumor
  • Disability prior to the presenting stroke
Show all 26Show fewer
  • Standard contraindications to IV alteplase within 3 hours of symptom onset, including:
  • Head trauma, myocardial infarction, or previous stroke within the previous 3 months
  • Gastrointestinal or urinary tract hemorrhage within the previous 21 days
  • Major surgery within the previous 14 days
  • Arterial puncture at non-compressible site within the previous 7 days
  • Any history of ICH with the exception of those less than (<) 5 chronic microbleeds on MRI
  • Elevated blood pressure defined by systolic blood pressure >185 millimeters of mercury (mm Hg) or diastolic blood pressure >110 mm Hg, or treatments requiring aggressive measures to achieve acceptable levels
  • Treatment with unfractioned heparin within past 48 hours and activated partial thromboplastin time outside normal range
  • Blood glucose <50 milligrams per deciliter (mg/dL)
  • International normalized ratio >1.7
  • Platelet count <100,000 per cubic millimeter (/mm^3)
  • Treatment with a direct thrombin inhibitor (dabigatran) or a factor Xa inhibitor (apixaban, rivaroxaban, edoxaban) within the last 48 hours
  • Allergic reaction to study drug, aspirin, or nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Females of childbearing age who are known to be pregnant and/or lactating
  • Inability to swallow, which would prevent oral intake of aspirin or aspirin placebo tablet
  • Other serious, advanced, or terminal illness that would confound the clinical outcome at 90 days
  • Current or recent (within 3 months) participation in another investigational drug treatment protocol
  • Anticipated inability to obtain 3-month follow-up assessments
  • Previous enrollment in PRISMS
  • Any other condition deemed by the investigator that would pose hazard to the participant with alteplase treatment

Trial locations and contacts

88 sites in 1 country.

88 sites in 1 country

United States88 sites
  • Akron General Medical Center

    Akron, Ohio, 44307

  • Lehigh Valley Hospital

    Allentown, Pennsylvania, 18105

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294-3300

  • Nova Clinical Research, LLC

    Bradenton, Florida, 34209

  • SUNY Downstate Medical Center.

    Brooklyn, New York, 11203

  • Lutheran Medical Center

    Brooklyn, New York, 11220

  • Buffalo General Medical Center

    Buffalo, New York, 14203

  • University of North Carolina At Chapel Hill

    Chapel Hill, North Carolina, 27514

  • Medical University of South Carolina; MSC 300

    Charleston, South Carolina, 29425

  • Chattanooga Center for Neurologic Research

    Chattanooga, Tennessee, 37404

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612-3244

  • University of Cincinnati

    Cincinnati, Ohio, 45203-0542

  • West Hospital

    Cincinnati, Ohio, 45211

  • The Christ Hospital

    Cincinnati, Ohio, 45219

  • Jewish Hospital

    Cincinnati, Ohio, 45236

  • Anderson Hospital

    Cincinnati, Ohio, 45255

  • Case Western Reserve University

    Cleveland, Ohio, 44109

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • University of Missouri Health Care

    Columbia, Missouri, 65212

  • University of South Carolina School of Medicine

    Columbia, South Carolina, 29203-7606

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Associated Neurologists PC

    Danbury, Connecticut, 06810

  • Wright State University

    Dayton, Ohio, 45409

  • Detroit Receiving Hospital

    Detroit, Michigan, 48201

  • St. Elizabeth Edgewood; Cancer Care Center" for Account St. Elizabeth Edgewood

    Edgewood, Kentucky, 41017

  • University of Louisville

    Elizabethtown, Kentucky, 42791

  • Alexian Brothers Neuroscience Institute

    Elk Grove Village, Illinois, 60007

  • Colorado Neurological Institute

    Englewood, Colorado, 80113

  • Inova Fairfax Hospital

    Fairfax, Virginia, 22031

  • Associated Neurologists of Southern CT PC

    Fairfield, Connecticut, 06824

  • Fairfield Hospital

    Fairfield, Ohio, 45014

  • St. Elizabeth Florence

    Florence, Kentucky, 41042

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Neurologic Consultants, P.A.

    Fort Lauderdale, Florida, 33308

  • St. Elizabeth Fort Thomas

    Fort Thomas, Kentucky, 41075

  • Parkview Research Center

    Fort Wayne, Indiana, 46845

  • St. Jude Medical Center

    Fullerton, California, 92835

  • The Minneapolis Clinic of Neurology

    Golden Valley, Minnesota, 55422

  • Guilford Neurologic Associates

    Greensboro, North Carolina, 27401

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Valley Baptist Medical Center

    Harlingen, Texas, 78550

  • Hartford Hospital

    Hartford, Connecticut, 06102

  • Penn State Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Methodist Neurological Institute

    Houston, Texas, 77030

  • University Of Texas Health Science Center Houston

    Houston, Texas, 77030

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • University of Tennessee Medical Center

    Knoxville, Tennessee, 37920

  • Gunderson Health System

    La Crosse, Wisconsin, 54601

  • University of California San Diego

    La Jolla, California, 92093

  • Sparrow Health System

    Lansing, Michigan, 48909

  • University of Kentucky

    Lexington, Kentucky, 40536

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Medical Center of The Rockies

    Loveland, Colorado, 80538

  • Texas Tech Univ Health Sci Ctr

    Lubbock, Texas, 79430

  • University of Wisconsin

    Madison, Wisconsin, 53792

  • University of Miami Miller School of Medicine; Clinical Reseach Building

    Miami, Florida, 33136

  • West Virginia University Hospital

    Morgantown, West Virginia, 26506

  • Ichan School of Medicine at Mount Sinai

    New York, New York, 10029

  • Columbia University Medical Center

    New York, New York, 10032

  • Christiana Care Health Services; Sponsor Programs Ammon Education Center

    Newark, Delaware, 19718-0002

  • Hoag Memorial Hospital

    Newport Beach, California, 92658

  • The Neurology And Pain Clinic

    Orangeburg, South Carolina, 29118

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Temple University Hospital

    Philadelphia, Pennsylvania, 19140

  • Albert Einstein Healthcare Network

    Philadelphia, Pennsylvania, 19141

  • Banner Good Samaritan Medical Center

    Phoenix, Arizona, 85006

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • University of Pittsburgh Cancer Institute

    Pittsburgh, Pennsylvania, 15219

  • St Joesph Mercy Hospital Oakland

    Pontiac, Michigan, 48341

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Providence Saint Vincent's Medical Center

    Portland, Oregon, 97225

  • Northwest Hospital Center

    Randallstown, Maryland, 21133

  • Renown Health; Renown Institute for Neurosciences

    Reno, Nevada, 89502

  • Beaumont Hospital

    Royal Oak, Michigan, 48073

  • University Of Utah

    Salt Lake City, Utah, 84108

  • University Hospital San Antonio

    San Antonio, Texas, 78229

  • University of California Los Angeles

    Santa Monica, California, 90404

  • Swedish Medical Center

    Seattle, Washington, 98122

  • Washington University

    St Louis, Missouri, 63128

  • Overlook Hospital

    Summit, New Jersey, 07902

  • University of Toledo Medical Center

    Toledo, Ohio, 43614

  • Shore Neurology

    Toms River, New Jersey, 08755

  • University of Arizona

    Tucson, Arizona, 85724-5030

  • Wake Forest Baptist Medical Center

    Winston-Salem, North Carolina, 27157

  • York Hospital

    York, Pennsylvania, 17403

Other trials in United States

About this study

Official title: A Phase IIIB, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Alteplase in Patients With Mild Stroke: Rapidly Improving Symptoms and Minor Neurologic Deficits (PRISMS)

PRISMS is a double-blind, multicenter, randomized, Phase IIIb study to evaluate the efficacy and safety of intravenous (IV) alteplase in participants with mild acute ischemic strokes that do not appear to be clearly disabling. Participants will be randomized in a 1:1 ratio to receive within 3 hours of last known well time either 1) one dose of IV alteplase and one dose of oral aspirin placebo or 2) one dose of IV alteplase placebo and one dose of oral aspirin 325 milligrams (mg).

Conditions
Stroke
Being tested
Alteplase, Alteplase Placebo, Aspirin, Aspirin Placebo
Medical subject headings
Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlteplaseDrug

    Also called Activase; RO5532960

    Single dose of alteplase will be administered at 0.9 milligrams per kilogram (mg/kg) IV (maximal dose of 90 mg).

  • Alteplase PlaceboDrug

    Single dose of alteplase placebo will be administered as IV injection.

  • AspirinDrug

    Single dose of aspirin will be administered at 325 mg orally.

  • Aspirin PlaceboDrug

    Single dose of aspirin placebo will be administered orally.

Study groups in NCT02072226
Study groupRoleWhat they receive
Alteplase Placebo + AspirinActive comparatorParticipants will receive single dose of IV alteplase placebo and aspirin orally.
Receives: Drug: Alteplase Placebo; Drug: Aspirin
Alteplase + Aspirin PlaceboExperimentalParticipants will receive single dose of IV alteplase and aspirin placebo orally.
Receives: Drug: Alteplase; Drug: Aspirin Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 or 1 at Day 90

    mRS score was determined by the investigator. The mRS is a 7 point scale (0-6) with 0: No symptoms at all, 1: No significant disability despite symptoms, able to carry out all usual duties and activities, 2: Slight disability, unable to carry out all previous activities but able to look after own affairs without assistance, 3: Moderate disability requiring some help, but able to walk without assistance, 4: Moderately severe disability, unable to walk without assistance and unable to attend to own bodily needs without assistance, 5: Severe disability, bedridden, incontinent and requiring constant nursing care and attention, 6: death prior to Day 90. Reported is the percentage of participants with scores of 0 or 1 on the mRS.

    Measured: Day 90

Secondary outcomes (8)
  1. Distribution of Participants Across the Ordinal mRS

    mRS score was determined by the investigator. The mRS is a 7 point scale (0-6) with 0: No symptoms at all, 1: No significant disability despite symptoms, able to carry out all usual duties and activities, 2: Slight disability, unable to carry out all previous activities but able to look after own affairs without assistance, 3: Moderate disability requiring some help, but able to walk without assistance, 4: Moderately severe disability, unable to walk without assistance and unable to attend to own bodily needs without assistance, 5: Severe disability, bedridden, incontinent and requiring constant nursing care and attention, 6: death before Day 90. Reported are the percentages of participants for all scores on the mRS.

    Measured: Day 90

  2. Percentage of Participants With Global Favorable Recovery on mRS, NIHSS, BI, and GOS

    Global favorable recovery is an integrated assessment of participants who meet the following: mRS Score 0-1, National Institutes of Health Stroke Scale (NIHSS) Score 0-1, Barthel Index [BI] greater than or equal to 95, and Glasgow Outcome Scale [GOS] equal to 1. mRS Score 0-1: 0= No symptoms at all, 1= No significant disability despite symptoms, able to carry out all usual duties and activities. NIHSS Score 0-1: 0= No stroke symptoms and 1= Minor stroke symptoms. BI is a 10 question index with a total score range of 0-100 with 100 being the best outcome. GOS =1: Good recovery. Reported here are the percentages of participants who achieved a favorable score on each of these scales.

    Measured: Day 90

  3. Percentage of Participants With Symptomatic Intracranial Hemorrhage (ICH )

    ICH was considered symptomatic if it was not seen on computed tomography (CT) or magnetic resonance imaging (MRI) scan at baseline and any neurologic decline was attributed to it by the local investigator. To detect intracranial hemorrhage, neuroimaging (CT or MRI) scan was performed at 22 to 36 hours after study drug administration.

    Measured: Within 36 hours after study drug administration on Day 1

  4. Percentage of Participants With Any ICH

    To detect ICH, neuroimaging (CT or MRI) scan was performed at 22 to 36 hours after study drug administration.

    Measured: Within 36 hours after study drug administration on Day 1

  5. Overall Mortality

    Reported here is the percentage of participants who died due to any cause during the study.

    Measured: From baseline to Day 90

  6. Percentage of Participants Who Died Due to Stroke and Neurological Disorders

    Reported here is the percentage of participants who died due to stroke and neurological disorders.

    Measured: From baseline to Day 90

  7. Percentage of Participants With Adverse Events

    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

    Measured: From baseline up to Day 90: Non-serious adverse events were collected through the Day 30 visit. Serious adverse events were collected through the end of study at Day 90.

  8. Percentage of Participants With Serious Adverse Events

    A serious adverse event (SAE) was defined as any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.

    Measured: From baseline to Day 90

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Feb 2014 (estimated)
  2. Study start31 May 2014
  3. Primary completion22 Mar 2017
  4. Study completion22 Mar 2017

Why it stopped: The study was terminated due to slow enrollment.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
313 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02072226
Sponsor's protocol ID
ML29093
Acronym
PRISMS
Status last verified
Jun 2018
First submitted
24 Feb 2014
Last updated
3 Jul 2018
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Khatri P, Kleindorfer DO, Devlin T, Sawyer RN Jr, Starr M, Mejilla J, Broderick J, Chatterjee A, Jauch EC, Levine SR, Romano JG, Saver JL, Vagal A, Purdon B, Devenport J, Pavlov A, Yeatts SD; PRISMS Investigators. Effect of Alteplase vs Aspirin on Functional Outcome for Patients With Acute Ischemic Stroke and Minor Nondisabling Neurologic Deficits: The PRISMS Randomized Clinical Trial. JAMA. 2018 Jul 10;320(2):156-166. doi: 10.1001/jama.2018.8496.

    PubMed 29998337
  • Zhao W, Mu Y, Tayama D, Yeatts SD. Comparison of statistical and operational properties of subject randomization procedures for large multicenter clinical trial treating medical emergencies. Contemp Clin Trials. 2015 Mar;41:211-8. doi: 10.1016/j.cct.2015.01.013. Epub 2015 Jan 29.

    PubMed 25638754
  • Choi JC, Jang MU, Kang K, Park JM, Ko Y, Lee SJ, Cha JK, Kim DH, Park SS, Park TH, Lee KB, Lee J, Kim JT, Cho KH, Yu KH, Oh MS, Lee BC, Cho YJ, Kim DE, Lee JS, Lee J, Gorelick PB, Bae HJ. Comparative effectiveness of standard care with IV thrombolysis versus without IV thrombolysis for mild ischemic stroke. J Am Heart Assoc. 2015 Jan 27;4(1):e001306. doi: 10.1161/JAHA.114.000596.

    PubMed 25628404

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Alteplase and Aspirin in people with Stroke, run by Genentech, Inc. at 88 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 88 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 or 1 at Day 90 (time frame: Day 90). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02072226, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2018.

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